PROJECT ABSTRACT Among nearly 1 million HIV-infected children receiving antiretroviral treatment (ART), as many as 40% of those living in resource limited settings have not achieved virologic suppression. Kenya, a UNAIDS fast-track and PEPFAR priority country, has an estimated 98,000 children aged 0-14 years living with HIV. Virologic suppression is achieved by only 65% of Kenyan children on ART translating to only 38% of the final UNAIDS 90-90-90 goal for population-level viral suppression. Feasible, scalable and cost-effective approaches to maximizing durability of 1st line ART and ensuring viral load (VL) suppression in HIV-infected children are urgently needed. The goal of this pilot study is to determine the feasibility and impact of point-of-care (POC) VL drug resistance mutation (DRM) testing to improve VL suppression in children on 1st line ART within a PEPFAR-funded HIV care and treatment program in Kenya. The proposed research is a randomized, controlled study to pilot the use of POC VL and DRM testing in children aged 1-14 years on 1st line ART at three sites with on-site access to GeneXpert? technology. Children enrolling at each site will be randomized 1:1 to intervention (POC VL and targeted DRM testing) vs. control (standard-of-care) arms and followed for 12 months. The proposed study will be conducted in PEPFAR-supported HIV treatment facilities in western Kenya, a PEPFAR priority country. This pilot study will evaluate two critical components related to viral suppression in children via: 1) POC VL testing (Aim 1) and 2) targeted DRM testing (Aim 2) among children on 1st line ART. Our primary outcome is the proportion of children achieving VL suppression 12 months after POC VL testing implementation, with a secondary outcome of time to viral suppression in those children not suppressed or initiating ART. This pilot study helps build the foundation for a future adaptive trial which packages optimized POC VL and DRM monitoring algorithms with sociobehavioral behavioral interventions to maximize VL suppression rates in children on 1st line ART and facilitate timely switch to 2nd line ART in resource-limited settings. This pilot study will provide critical information on the impact of POC VL testing on viral suppression among children on 1st line ART in a resource-limited setting. It will additionally show current patterns and impact of DRM testing among children undergoing routine VL monitoring. Findings from this pilot will inform the development of an adaptive clinical trial which evaluates the impact of combination interventions, including POC VL and DRM testing at programmatic scale, facility- and community-based care packages, and the cost-effectiveness of implementing each strategy in achieving viral suppression. This proposal directly addresses the urgent need to find interventions to maximize viral suppression among children on ART and achieve the UNAIDS 90-90-90 goals.